The aim of this project is to gain a greater understanding of the psychobiology of schizophrenia. Clinical research for this project is carried out on the 4-East Nursing Unit of the Clinical Center. Patients with DSM-III diagnosed schizophrenia are studied during a several month research period during which time they are treated under double-blind conditions with neuroleptic and placebo medications. A major goal of this project is to gain a better understanding of the mechanism of action of neuroleptic drugs and a profile of which symptoms are most responsive to drug treatment. Data from a preliminary study have shown that neuroleptic-induced, time-dependent decreases in levels of plasma HVA (a major dopamine metabolite) are correlated with antipsychotic drug response. These data suggest that neuroleptic effects on dopamine release are related to clinical improvement. These findings are being more fully examined using hourly blood sampling during 24-hour studies, and may be a useful model for studying pharmacologic profiles of potential antipsychotic drugs. Preliminary investigations into the possible therapeutic effect of the calcium channel blocker, verapamil, are underway since dopamine release and postsynaptic transmission are calcium dependent phenomena.